HLA-A*02:07 is a protective allele for EBV negative and a susceptibility allele for EBV positive classical Hodgkin lymphoma in China

HLA-A2 protects from EBV+ classical Hodgkin lymphoma (cHL) in Western Europe, but it is unknown whether this protective effect also exists in the Chinese population. We investigated the association of HLA-A2 and specific common and well documented HLA-A2 subtypes with EBV stratified cHL patients (n = 161) from the northern part of China. Quantitative-PCR and sequence-based subtyping was performed to identify HLA-A2 positive samples and their subtypes. 67 (42%) of the cHL patients were EBV+. There were no significant differences in percentages of HLA-A2 positivity between cHL and controls (65% vs 66%) and between EBV+ and EBV− cHL patients (70% vs 61%). The frequency distribution of HLA-A2 subtypes was significantly different between EBV stratified cHL subgroups and controls. This difference was most striking for the HLA-A*02:07 type with a frequency of 38% in EBV+ cHL, 8% in EBV− cHL and 20% in controls. Significant differences were also observed for the HLA-A*02:07, HLA-A2 (non-02:07) and the A2-negative typings between EBV+ cHL vs controls (p = 0.028), EBV− cHL vs controls (p = 0.045) and EBV+ vs EBV− cHL cases (p = 2×10⁻⁵). In conclusion, HLA-A*02:07 is a predisposing allele for EBV+ cHL and a protective allele for EBV− cHL in the northern Chinese population.     

Mps1 phosphorylates Borealin to control Aurora B activity and chromosome alignment

Maintenance of chromosomal stability relies on coordination between various processes that are critical for proper chromosome segregation in mitosis. Here we show that monopolar spindle 1 (Mps1) kinase, which is essential for the mitotic checkpoint, also controls correction of improper chromosome attachments. We report that Borealin/DasraB, a member of the complex that regulates the Aurora B kinase, is directly phosphorylated by Mps1 on residues that are crucial for Aurora B activity and chromosome alignment. As a result, cells lacking Mps1 kinase activity fail to efficiently align chromosomes due to impaired Aurora B function at centromeres, leaving improper attachments uncorrected. Strikingly, Borealin/DasraB bearing phosphomimetic mutations restores Aurora B activity and alignment in Mps1-depleted cells. Mps1 thus coordinates attachment error correction and checkpoint signaling, two crucial responses to unproductive chromosome attachments.     

Heterogeneous adaptive trajectories of small populations on complex fitness landscapes

Background

Small populations are thought to be adaptively handicapped, not only because they suffer more from deleterious mutations but also because they have limited access to new beneficial mutations, particularly those conferring large benefits.

Methodology/Principal Findings

Here, we test this widely held conjecture using both simulations and experiments with small and large bacterial populations evolving in either a simple or a complex nutrient environment. Consistent with expectations, we find that small populations are adaptively constrained in the simple environment; however, in the complex environment small populations not only follow more heterogeneous adaptive trajectories, but can also attain higher fitness than the large populations. Large populations are constrained to near deterministic fixation of rare large-benefit mutations. While such determinism speeds adaptation on the smooth adaptive landscape represented by the simple environment, it can limit the ability of large populations from effectively exploring the underlying topography of rugged adaptive landscapes characterized by complex environments.

Conclusions

Our results show that adaptive constraints often faced by small populations can be circumvented during evolution on rugged adaptive landscapes.     

Complex oligomeric structure of a truncated form of DdrA: a protein required for the extreme radiotolerance of Deinococcus

In order to preserve their genome integrity, organisms have developed elaborate tactics for genome protection and repair. The Deinococcus radiodurans bacteria famous for their extraordinary tolerance toward high doses of radiations or long period of desiccation, possess some specific genes with unknown function which are related to their survival in such extreme conditions. Among them, ddrA is an orphan gene specific of Deinococcus genomes. DdrA, the product of this gene was suggested to be a component of the DNA end protection system. Here we provide a three-dimensional reconstruction of the Deinococcus deserti DdrA((1-160)) by electron microscopy. Although not functional in vivo, this truncated protein keeps its DNA binding ability at the wild-type level. DdrA((1-160)) has a complex three-dimensional structure based on a heptameric ring that can self-associate to form a larger molecular weight assembly. We suggest that the complex architecture of DdrA plays a role in the substrate specificity and favors an efficient DNA repair.     

RAPD and ISSR markers indicate diminished gene flow due to recent fragmentation of Polylepis australis woodlands in central Argentina

Two Polylepis australis BITT. populations differing in size were examined with the aim of determining future sampling strategies; assessing levels of genetic diversity and checking whether trees of different ages might vary in their genetic structure due to the effects of fragmentation. RADP and ISSR gave similar values of diversity. A re-sampling technique showed that for P. australis, 10 trees and 20 markers were enough to produce an unbiased estimator of heterozygosity. AMOVA suggested differences in allele frequencies between young and old trees in the small population (p = 0.052), but not in a large population (p = 0.864); suggesting that gene flow between the areas diminished in relatively recent times. This assumption is supported by the fact that allele frequencies among both woodlands were significantly different between the young (p < 0.0001), but not the older trees (p = 0.87).     

The Restoration of Degraded Mountain Woodlands: Effects of Seed Provenance and Microsite Characteristics on Polylepis australis Seedling Survival and Growth in Central Argentina

South American high‐mountain ecosystems are greatly influenced by human disturbance. In the mountains of Córdoba, Argentina, Polylepis australis (Rosaceae) woodlands are currently highly fragmented and subject to extensive burning and livestock grazing, resulting in severe changes of habitat characteristics, which hamper natural regeneration. In order to find out how to achieve successful reforestation, we compared P. australis seedling survival and growth and the development of a shrubby habit for two seed provenances and different planting microsites. Survival of planted seedlings after 5 years was 70%, with most deaths (19%) in the first year and declining mortality with ongoing establishment. Survival did not show any relationship with seed provenance or microsite characteristics. Height growth averaged 34.6 ± 1.2 cm in 5 years. Seedlings produced from seeds collected in a well‐preserved woodland grew taller and showed a higher tendency for development of shrubby habit than those produced from seeds collected in a degraded woodland. Seedlings planted in more degraded microsites with exposed soil or rock due to past grazing pressure grew less and developed a more shrubby habit than those planted in better preserved microsites. Our results show that restoration of degraded areas with P. australis is possible and that there is potential to improve restoration success with a careful selection of seed provenance and planting microsites.     

Bringing science and pragmatism together a tiered approach for modelling toxicological impacts in LCA

Goal, Scope and Background  The EU 5^th framework project OMNIITOX will develop models calculating characterisation factors for assessing the potential toxic impacts of chemicals within the framework of LCA. These models will become accessible through a web-based information system. The key objective of the OMNIITOX project is to increase the coverage of substances by such models. In order to reach this objective, simpler models which need less but available data, will have to be developed while maintaining scientific quality. Methods. Experience within the OMNIITOX project has taught that data availability and quality are crucial issues for calculating characterisation factors. Data availability determines whether calculating characterisation factors is possible at all, whereas data quality determines to what extent the resulting characterisation factors are reliable. Today, there is insufficient knowledge and/or resources to have high data availability as well as high data quality and high model quality at the same time. Results  The OMNIITOX project is developing two inter-related models in order to be able to provide LCA impact assessment characterisation factors for toxic releases for as broad a range of chemicals as possible: 1) A base model representing a state-of-the-art multimedia model and 2) a simple model derived from the base model using statistical tools. Discussion. A preliminary decision tree for using the OMNIITOX information system (IS) is presented. The decision tree aims to illustrate how the OMNIITOX IS can assist an LCA practitioner in finding or deriving characterisation factors for use in life cycle impact assessment of toxic releases. Conclusions and Outlook  Data availability and quality are crucial issues when calculating characterisation factors for the toxicity impact categories. The OMNIITOX project is developing a tiered model approach for this. It is foreseen that a first version of the base model will be ready in late summer of 2004, whereas a first version of the simple base model is expected a few months later.